Session M5: General Bio Fluids II

Microjets of citrus fruit

The rupture of oil glands in the citrus exocarp is a common experience to the discerning citrus consumer. When peeled, oil cavities housed with the citrus exocarp often rupture outwardly in response to externally applied bending stresses. Bending of the peel compresses the soft material surrounding the glands, the albedo, increasing fluid pressure. Ultimately, the fluid pressure exceeds the failure strength of the outermost membrane, the flavedo. The ensuing high-velocity discharge of oil and exhaustive emptying of oil glands creates a novel method for jetting small quantities of the aromatic and volatile oil. We compare the jetting behavior across five citrus hybrids through high-speed videography and material testing of exocarps. The jetting oil undergoes an initial acceleration surpassing 5,000 gravities, reaching velocities in excess of 10 m/s. Film of citrus jets and mimicking jets in the lab reveal their high level of instability is caused by irregular and non-circular orifice geometry. Through material characterization and bending simulations, we rationalize the combination of material properties necessary to generate the internal gland pressures required for explosive dispersal.   

Scaled experiments for improving diagnosis of pathological lower-airway obstruction

Many lung diseases, such as asthma and chronic obstructive pulmonary disease, are characterized by obstructed airflow, particularly, in the lower airway branches in the lung. Existing diagnostic tools cannot detect some diseases due to a lack of instrumentation capable of resolving the flow in the lower airways. Recent developments in MRI techniques using hyperpolarized $^3$He now permit measurement of velocity profiles within the trachea. Motivated by these advances, we aim to provide a better understanding of the connection between lower-airway obstruction and velocity profiles within the trachea. Specifically, we asked whether the flow deficits created by lower-airway obstructions could be detected in the trachea to permit diagnosis of the pathology. To test this idea, we used refractive index-matched materials to construct a scaled, patient-specific, transparent lung model, and coupled it to 5 independently controlled piston pumps that could generate arbitrary flow histories (healthy or diseased) for the 5 different lung lobes. Results obtained by stereo PIV within various regions of the airway network will be presented documenting the system performance and examining the detectability of under-performing lobes within the tracheal flow profile.   

Stochastic Modeling of the Clathrin-dependent and -independent Endocytic Pathways

Endocytosis is one of the important processes that bioparticles use to enter the cells. During endocytosis the membrane-bound vesicles are formed by the invagination of plasma membrane as a result of interactions among many proteins and cytoskeletons. The clathrin-mediated endocytosis is one of the most significant form of endocytosis, where the dynamic assembly of clathrin-coated pits play a critical role. While herpes simplex virus-1 has recently shown to infect cell by a novel phagocytosis-like endocytic pathway where actin polymerization may facilitate the viral entry. In this work, we propose a stochastic model for both clathrin-dependent and --independent endocytic pathways based on Monte Carlo simulations. The important roles of clathrin coating and actin cytoskeleton as well as the impact of other biological parameters are studied. Our preliminary results indicate that there exist an intermediate particle size and ligand density that maximize the internalization efficiency. Below a critical size or surface ligand density, it is difficult for the entry of a single particle, which means clustering may needed for more efficient internalization. We also find that lower membrane bending rigidity may help promote the bioparticle entry.   

Using droplet-on-demand based printing to guide self-assembly in a peptide-protein based bioink

Tissue engineering aims to capture details of the extracellular matrix (ECM) that stimulate tissue regeneration. Advanced biofabrication techniques have enabled structural complexity, however they are restricted by the choice of material due to stringent printing requirements, leading to a lack of nanoscale control and molecular versatility. In this project, we exploit the dynamics of droplet fluid interactions combined with the co-assembly of peptide amphiphiles (PAs) with biomolecules/proteins to develop a new approach to droplet-based biofabrication. A custom-made droplet generator was developed and used to controllably dispense droplets of PA into a protein solution resulting in gel formation within milliseconds. Taking advantage of the interfacial and inertial forces during the droplet/liquid interaction, it is possible to control the co-assembly kinetics, to give rise to aligned or disordered nanofibers, hydrogel structures of different geometries and sizes, surface topographies, and higher-ordered structures made from multiple hydrogels. The process allows multiple cell types to be spatially distributed on the outside or embedded within the ECM mimetic scaffolds, whilst exhibiting high cell viability ($>$ 88 \%).   

Fibre-reinforced hydrogels for tissue engineering

Tissue engineers aim to grow replacement tissues in vitro to replace those in the body that have been damaged through age, trauma or disease. One approach is to seed cells within a scaffold consisting of an interconnected 3D-printed lattice of polymer fibres, cast in a hydrogel, and subject the construct (cell-seeded scaffold) to an applied load in a bioreactor. A key question is to understand how this applied load is distributed throughout the construct to the mechanosensitive cells. To address this, we exploit the disparate length scales (small inter-fibre spacing compared with construct dimensions). The fibres are treated as a linear elastic material and the hydrogel as a poroelastic material. We employ homogenisation theory to derive equations governing the material properties of a periodic, elastic-poroelastic composite. To validate the mobel, model solutions are compared to experimental data describing the unconfined compression of the fibre-reinforced hydrogels. The model is used to derive the bulk mechanical properties of a cylindrical construct of the composite material for a range of fibre spacings, and the local mechanical environment experienced by cells embedded within the construct is determined.   

A coarse-grained model for suspensions of inextensible, flexible fibers

The modeling of inextensible flexible fibers immersed in a fluid is a challenging computational problem. Although several well-developed computational methods exist, fibers do not always occur in isolation: in many biologically and industrially relevant contexts, there are many fibers, and the fluid the fibers are moving through may be best thought of as a porous media with an anisotropic porosity that depends on the configuration of those fibers. We develop a coarse-grained model for these systems, and use it to investigate fluid mediated elastic relaxation, buckling instabilities, and flow rectification.   

Dynamics of Active Microfilaments

Soft elastic filaments are ubiquitous in natural and artificial systems at various length scales, and their interactions within and between filaments and their environments provide a persistent source of curiosity due to both the complexity of their behaviors and the relative mathematical simplicity of their structures. Specifically, a deeper understanding of the dynamic characteristics of microscopic filaments in viscous fluids is relevant to many biophysical and physiological processes. Here we start with the Cosserat model that allows all six possible modes of deformation for an elastic rod, and focus on the case of inextensible filaments submerged in viscous fluids by ignoring inertial effects and using local resistive force theory for fluid-filament interactions. We verify our simulations against special analytic solutions and present some results on the active internal control of cilia and flagella motion. We conclude by commenting on the utility of this general framework for studying other cellular and sub-cellular physical processes such as systems involving protein filaments.   

Coarse-grained Simulations of Substrate Export through Multidrug Efflux Transporter AcrB

The treatment of bacterial infectious diseases hampered by the overexpression of multidrug resistance (MDR) systems. The MDR system actively pumps the antibiotic drugs as well as other toxic compounds out of the cells. During the pumping, AcrB (one of the key MDR components) undergoes a series of large-scale proton/substrate dependent conformational changes. In this work, we~implement a hybrid coarse-grained PACE force field that couples the united-atom protein model with the coarse-grained MARTINI water/lipid, to investigate the conformational changes of AcrB. We first develop the substrate force field which is compatible with PACE, then we implement the force field to explore large scale structural changes of AcrB in microsecond simulations. The effects of the substrate and the protonation states of two key residues: Asp407 and Asp408, are investigated. Our results show that the drug export through AcrB is proton as well as substrate dependent. Our simulations explain molecular mechanisms of substrate transport through AcrB complex, as well as provide valuable insights for designing proper antibiotic drugs.   

Filter feeding mechanics of \textit{Hypophthalmichthys molitrix} regarding porous gill rakers

The silver carp \textit{(Hypophthalmichthys molitrix)} is a filter-feeding fish known to feed upon algal-growth in lakes, rivers, and aquacultures. The filter-feeding process centers on sponge-like membranes located in the carp’s pharynx supported by fused gill rakers (GRs), which can efficiently strain suspended food particles as small as 4 µm without clogging. Guided by the anatomy of the silver carp, scanning electron microscope (SEM) images of GRs, and video of the silver carp feeding, we have hypothesized that the filtration mechanism involves a pump-based biological function to capture food particles within the GRs. Dye visualization experiments were performed on a silver carp cadaver head, an excised GR sample, and on a scaled GR in vitro model - the Artificial Gill Raker (AGR). Measurements are performed for the AGR using laser Doppler velocimetry (LDV) and penetration pressure monitoring with a biologically-inspired pumping mechanism. The role of mucus in the retention and capture of food particles has also been explored through rheological measurements, and further experimentation is planned. Our motivation stems from the potential to develop bioinspired industrial-scale filtration technologies ranging from wastewater treatment to filtration in the food industry.   

Effects of branching morphology on flow for a single coral colony

Coral colony growth, morphology, and mass transfer all strongly depend on the local hydrodynamics. But the intra-colony hydrodynamics also strongly depends on the colony morphology. To understand these interdependent effects, three dimensional immersed boundary method simulations were performed in the LES framework for realistic Reynolds numbers between 5,000 and 15,000 for both densely (\textit{Pocillopora}) and loosely (\textit{Montipora}) branched coral colonies. The loosely branched corals (LBC) allow more flow penetration through their sparser branches than do densely branched corals (DBC). In contrast, DBCs present higher resistance to flow and divert more flow around the colony. In both cases, the front of the coral experiences higher velocity than the back, while the flow decreases rapidly along the coral for DBCs in comparison to LBCs. Furthermore, it has been observed that for high Reynolds number regimes, LBCs roughen their branch surfaces with protrusions to increase the thickness of boundary layer and reduce the incidence of breakage. To understand this phenomenon, models of LBCs were simulated with and without protrusions distributed on the branch surface.